A first-in-human clinical trial in adult patients with advanced non-small cell lung cancer of a personalised therapy targeting specific mutations that occur in all cancer cells within a single patient.

Phase 1

• Conditions: on-small cell lung cancer; MedDRA version: 21.1Level: PTClassification code 10001245Term: Adenosquamous cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10001247Term: Adenosquamous cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10001251Term: Adenosquamous cell lung cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10001254Term: Adenosquamous cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10023775Term: Large cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10023779Term: Large cell lung cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10023780Term: Large cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10029515Term: Non-small cell lung cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10029519Term: Non-small cell lung cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

• Registration Number: EUCTR2018-001005-85-DE
• Lead Sponsor: Achilles Therapeutics UK Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-09-14
• Last Update Posted: 18 June 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Inclusion criteria will apply at multiple timepoints.

Inclusion Criteria:
1. Patient must be between 18 and 75 years old at the screening visit.
2. Patient must have given written informed consent to participate in the study.
3. Patient must have histologically confirmed diagnosis of non-small cell lung cancer, which is considered to be smoking-related.
4. Patient is considered medically fit enough to undergo all study procedures and interventions: procedures to procure blood and tumour tissue, including a general anaesthetic if required, and to receive fludarabine, cyclophosphamide and IL-2 at protocol doses and schedules.
5. Patient is considered, in the opinion of the Investigator, capable of adhering to the protocol.
6. ECOG Performance Status 0-1.
7. Adequate organ function, indicated by the following laboratory parameters:
a. Haemoglobin = 10.0 g/dL.
b. White Blood Cell Count (WBC) = 3.0 x10^9/L.
c. Absolute Neutrophil Count (ANC) = 1.5 x10^9/L (without support of filgrastim (G-CSF)).
d. Platelets = 100 x10^9/L.
e. INR/PT and APTR/APTT < 1.5x UL, unless receiving therapeutic anticoagulation. Investigator discretion is required to ensure surgery is safe or that anticoagulants can be safely stopped.
f. AST or ALT = 2.5x ULN.
g. Bilirubin < 1.5x ULN (or < 3 x ULN in Gilbert’s Syndrome).
h. Creatinine clearance/estimated GFR = 50 mL/min.
8. Female patients who are of childbearing potential must agree to use a highly effective method of contraception during the study and for at least 12 months after the ATL001 infusion. Nonsterilised male participants who intend to be sexually active with a female partner of childbearing potential must use an acceptable method of contraception from the time of screening, throughout the duration of the study and for at least 6 months after the ATL001 infusion. Refer to Appendix G for pregnancy testing requirements in Germany. See Section 4.3 for details of acceptable methods of contraception.
In addition to a re-evaluation of criteria 1-8, the following inclusion criteria must also be met prior to tissue procurement:
9. To be eligible to enter this study for procurement, a patient must fall into one of the following
groups:
a. Patients with advanced stage (III-IV) NSCLC who have accessible sites of disease suitable for collection of adequate tissue for ATL001 manufacture prior to starting standard treatment.
b. Patients with advanced stage (III-IV) NSCLC who have received or are receiving standard treatments and have accessible sites of disease suitable for collection of adequate tissue for ATL001 manufacture.
c. Other patients with advanced stage disease for whom no other alternative approved treatments are available, may be considered on a case-by-case basis and should be discussed with the Sponsor prior to enrolment.
10. Anticipated life expectancy = 6 months at the time of tissue procurement.
In addition to a re-evaluation of criteria 1-8, the following inclusion criteria must also be met prior to lymphodepletion for treatment with ATL001:
11. Patients must have locally advanced unresectable or metastatic NSCLC and:
a. Whose disease has progressed or recurred following standard of care. This includes patients who have received a component of standard of care therapy as part of a previous clinical trial in first line treatment; or
b. Who are ineligible for, or who cannot tolerate, standard of care therapies. Patients who stop treatment due to immunotherapy toxicities do not need to progress in orde

Exclusion Criteria

Exclusion criteria will apply at multiple timepoints.

Exclusion Criteria:
1. Patients with known central nervous system (CNS) metastases that are untreated or symptomatic or progressing. Lesions should be clinically and radiologically stable for 2 months after treatment, as determined by MRI or CT evaluation, in line with accepted standard of care procedures, and should not require steroids.
2. Patients with hepatitis B or C, human immunodeficiency virus infection (HIV1/2), syphilis or HTLVI/II infection (see Section 6.1.1).
3. Patients who have never smoked (defined as having smoked < 100 cigarettes in their lifetime, per WHO criteria).
4. Patients for whom there is documented evidence of an actionable tumour driver oncogene mutation (EGFR, ALK or ROS-1) at the time of initial screening. Patients who have progressed on standard targeted therapies, or for whom no approved targeted treatments are available, are not excluded.
5. Patients with active, known, or suspected autoimmune disease requiring immunosuppressive treatments.
6. Patients requiring regular treatment with steroids at a dose higher than prednisolone 10 mg/day (or equivalent).
7. Patients with superior vena cava syndrome.
8. Patients with a current or recent history, as determined by the Investigator, of clinically significant, progressive, and/or uncontrolled renal, hepatic, haematological, endocrine, pulmonary, cardiac, gastroenterological or neurological disease. Additionally, the following criteria apply:
a. Patients with a Left Ventricular Ejection Fraction (LVEF) < 45%.
b. Patients with a history of coronary revascularization.
c. Patients with clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, 2° or 3° heart block.
d. Patients with a forced expiratory volume in one second (FEV1) of less than or equal to 60% of their predicted normal.
9. Patients with a history of immune mediated central nervous system toxicity that was caused by, or suspected to be caused by, immunotherapy.
10. Patients with a history of = Grade 2 diarrhoea/colitis caused by previous immunotherapy within 6 months of screening. Patients that have been asymptomatic for at least 6 months or have had a normal colonoscopy post-immunotherapy (with uninflamed mucosa by visual assessment following discontinuation of immune suppression other than permitted modified release steroids) are not excluded.
11. Patients who are pregnant or breastfeeding.
12. Patients who have undergone major surgery in the previous 3 weeks.
13. Patients with an active concurrent cancer or a history of cancer within the past 3 years (except for in situ carcinomas, early prostate cancer with normal PSA or non-melanomatous skin cancers).
14. Patients with a history of organ transplantation.
15. Patients who have previously received any investigational cell or gene therapies.
16. Patients with contraindications for cyclophosphamide, fludarabine and IL-2 at per protocol doses (see Investigator’s Brochure for details).
17. Patients who have received any cytotoxic chemotherapy or anti-angiogenesis agent within the 3 weeks prior to tissue and blood procurement.
18. Patients with evidence of disease progression at the first scan after commencing standard first line therapy (i.e. primary refractory disease), unless responsive to subsequent lines of therapy. Patients who are refractory to pembrolizumab monotherapy are not excluded.
19. Patients with a confir

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified